Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 602-927-1 | CAS number: 123312-89-0
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Neurotoxicity
Administrative data
- Endpoint:
- neurotoxicity, other
- Remarks:
- Developmental neurotoxicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 5 Nov 2002 to12 Sep 2003
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 003
- Report date:
- 2003
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.6300 (Developmental Neurotoxicity Study)
- Version / remarks:
- August 1998
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 6-methyl-4-[(E)-[(pyridin-3-yl)methylidene]amino]-2,3,4,5-tetrahydro-1,2,4-triazin-3-one
- EC Number:
- 602-927-1
- Cas Number:
- 123312-89-0
- Molecular formula:
- C10H11N5O
- IUPAC Name:
- 6-methyl-4-[(E)-[(pyridin-3-yl)methylidene]amino]-2,3,4,5-tetrahydro-1,2,4-triazin-3-one
Constituent 1
Results and discussion
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Remarks:
- Maternal toxicity
- Effect level:
- 100 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- Dose descriptor:
- NOEL
- Remarks:
- Developmental neurotoxicity
- Effect level:
- 500 ppm (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- behaviour (functional findings)
- neuropathology
Target system / organ toxicity
- Critical effects observed:
- no
Any other information on results incl. tables
Maternal toxicity observed at 2500 ppm was more severe than anticipated. Marked effects on body weight, body weight gain and food consumption were seen during gestation and early lactation. Of the first 15 dams fed 2500 ppm, two were killed at the time of parturition due to adverse clinical signs (hunched posture, piloerection and subdued behaviour) and body weight loss. One of the second set of 15 females was killed due to parturition difficulties. In addition, there was high neonatal mortality with 4 out of 13 dams with whole litter losses and 31% live born pups either dead or missing by day 5 post-partum. This dose level was, therefore, considered to be too high based on maternal toxicity and high pup mortality, which would result in an insufficient number of pups to allow a meaningful evaluation of developmental neurotoxicity. Therefore, the group was terminated on 20 December 2002. At a subsequent meeting with the members of the Health Effects Division of the EPA, the Agency scientists agreed that the loss of this top dose level should not preclude a meaningful evaluation of the developmental neurotoxicity potential of the technical test material.
There were no adverse clinical signs or treatment-related effects in the functional observation battery on days 10 and 17 of gestation and days 2 and 9 of lactation for dams fed 500 or 100 ppm.
At 500 ppm, parent females had lower growth during late gestation (approximately 10% lower body weight than control), together with lower food consumption (7% lower than control) during week 3 of gestation. Body weightpost-partumwas similar to controls, although food consumption was lower between days 1 and 5.
There were 5 whole litter losses at 500 ppm. Although day 1 litter size, total litter weight and pup body weights for days 1-5 were unaffected, day 5 (pre-cull) litter size and total litter weight and the proportion of pups surviving during days 1-5 (pre-cull) were all slightly lower than control. There was an increase in the number of pups/litters with pups 'missing presumed dead' compared with control. The percentage of live born pups dead or missing by day 5 post-partum (31.8%) was the same as that seen at 2500 ppm.
Maternal body weight and food consumption during the dosing period was unaffected at 100 ppm. There was no effect on reproductive performance, litter size, survival, total litter weight or pup body weight to day 5 (pre-cull) at 100 ppm.
There were no effects of maternal treatment with technical test material at 100 or 500 ppm on body weight, developmental landmarks, functional observation battery, locomotor activity, learning and memory, auditory startle, haematology, brain weight, brain morphometry and histopathology of the nervous system of the selected F1 animals.
At 2500 ppm, there was clear evidence of maternal toxicity as characterised by effects on Body weight and food consumption during both gestation and lactation, and high neonatal pup mortality, leading to insufficient pups available for a meaningful assessment of developmental neurotoxicity potential. Therefore, this dose level was terminated. Maternal treatment with 500 ppm technical test substance showed some evidence of maternal toxicity characterised by lower growth and food consumption during late gestation, together with neonatal mortality, including five whole litter losses and increased numbers of pups and litters with pups either 'missing presumed dead' or dead. Also observed were slight reductions, relative to controls, in day 5 (pre-cull) litter size and total litter weight and the proportion of pups surviving during days 1-5 (pre-cull). However, there were no effects on any of the observations that detect gross neurologic and behavioural abnormalities.
Applicant's summary and conclusion
- Conclusions:
- At 500 ppm, there were no effects on any of the observations that detect gross neurologic and behavioural abnormalities, therefore, 500 ppm is considered to be the no observed effect level for developmental neurotoxicity in F1 animals. The dose level 100 ppm is the no observed effect level for maternal toxicity.
- Executive summary:
The purpose of this study was to determine the potential for developmental neurotoxicity in the assessment and evaluation of the toxic characteristics the technical test material in rats. The potential functional and morphological hazards to the nervous system that may arise in the offspring when the test substance is administered orally, via diet, to the parent female during gestation and lactation, were investigated.This study was conducted according to US EPA 870.6300, Developmental Neurotoxicity Study. Groups of 30, time-mated, female Alpk:APfSD (Wistar-derived) rats were given diets containing 0, 100, 500 or 2500 ppm technical test material from day 7 of gestation through day 22 post-partum. The day of sperm positive vaginal smear was designated day 1 of gestation. Pups were allocated to the F1 phase of the study on post-partum day 5, separated from the dam on day 29 and allowed to grow to adulthood. Evaluations included observations to detect gross neurological and behavioural abnormalities, effects on motor activity, response to auditory startle, assessment of learning and memory, neuropathological evaluation, including brain morphometry and brain weights and haematology.
Maternal toxicity observed at 2500 ppm was more severe than anticipated. Marked effects on body weight, body weight gain and food consumption were seen during gestation and early lactation. Of the first 15 dams fed 2500 ppm, two were killed at the time of parturition due to adverse clinical signs (hunched posture, piloerection and subdued behaviour) and body weight loss. One of the second set of 15 females was killed due to parturition difficulties. In addition, there was high neonatal mortality with 4 out of 13 dams with whole litter losses and 31% live born pups either dead or missing by day 5 post-partum .This dose level was, therefore, considered to be too high based on maternal toxicity and high pup mortality, which would result in an insufficient number of pups to allow a meaningful evaluation of developmental neurotoxicity. Therefore, the group was terminated on 20 December 2002. At a subsequent meeting with the members of the Health Effects Division of the EPA, the Agency scientists agreed that the loss of this top dose level should not preclude a meaningful evaluation of the developmental neurotoxicity potential of the technical test material.
There were no adverse clinical signs or treatment-related effects in the functional observation battery on days 10 and 17 of gestation and days 2 and 9 of lactation for dams fed 500 or 100 ppm.
At 500 ppm, parent females had lower growth during late gestation (approximately 10% lower body weight than control), together with lower food consumption (7% lower than control) during week 3 of gestation. Body weight post-partum was similar to controls, although food consumption was lower between days 1 and 5.
There were 5 whole litter losses at 500 ppm. Although day 1 litter size, total litter weight and pup body weights for days 1-5 were unaffected, day 5 (pre-cull) litter size and total litter weight and the proportion of pups surviving during days 1-5 (pre-cull) were all slightly lower than control. There was an increase in the number of pups/litters with pups 'missing presumed dead' compared with control. The percentage of live born pups dead or missing by day 5 post-partum (31.8%) was the same as that seen at 2500 ppm.
Maternal body weight and food consumption during the dosing period was unaffected at 100 ppm. There was no effect on reproductive performance, litter size, survival, total litter weight or pup body weight to day 5 (pre-cull) at 100 ppm.
There were no effects of maternal treatment with technical test material at 100 or 500 ppm on body weight, developmental landmarks, functional observation battery, locomotor activity, learning and memory, auditory startle, haematology, brain weight, brain morphometry and histopathology of the nervous system of the selected F1 animals.
At 2500 ppm, there was clear evidence of maternal toxicity as characterised by effects on Body weight and food consumption during both gestation and lactation, and high neonatal pup mortality, leading to insufficient pups available for a meaningful assessment of developmental neurotoxicity potential. Therefore, this dose level was terminated. Maternal treatment with 500 ppm technical test substance showed some evidence of maternal toxicity characterised by lower growth and food consumption during late gestation, together with neonatal mortality, including five whole litter losses and increased numbers of pups and litters with pups either 'missing presumed dead' or dead. Also observed were slight reductions, relative to controls, in day 5 (pre-cull) litter size and total litter weight and the proportion of pups surviving during days 1-5 (pre-cull). However, there were no effects on any of the observations that detect gross neurologic and behavioural abnormalities, therefore, 500 ppm is considered to be the no observed effect level for developmental neurotoxicity in F1 animals.The dose level 100 ppm is the no observed effect level for maternal toxicity.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.